ClinVar Miner

Submissions for variant NM_000143.4(FH):c.181A>C (p.Lys61Gln)

dbSNP: rs1660244612
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001230326 SCV001402801 uncertain significance Fumarase deficiency 2019-08-25 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamine at codon 61 of the FH protein (p.Lys61Gln). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FH-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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